HIV prevention requires improved identification of individuals at elevated behavioral risk. General health status and health-related quality of life (HRQOL) may reflect physical and mental health burdens linked to HIV risk behavior (HIVRB), but their relative predictive value is unclear. This study examined whether self-reported health and an unhealthy days–based HRQOL category were associated with HIVRB and whether HRQOL was a stronger predictor.

We conducted a cross-sectional analysis of the 2016-2022 Behavioral Risk Factor Surveillance System (BRFSS) data. The outcome HIVRB (yes vs. no) was defined as reporting at least one of the following: injection drug use, treatment for a sexually transmitted disease, or exchange of sex for money or drugs. Exposure 1 was a three-level self-reported health (SRH); Exposure 2 was a three-level unhealthy days–based HRQOL category. Weighted and adjusted logistic regression models were estimated, and effect modification was assessed.

In the overall sample (N=1,337,514), poorer SRH was associated with significantly greater weighted and adjusted odds (WAO) of HIVRB. Compared with excellent/very good health, good health was modestly associated (WAOR=1.10; 95%CI: 1.05–1.14), and fair/poor health showed stronger associations (WAOR=1.30; 95%CI: 1.23–1.37) with HIVRB. The HRQOL measure demonstrated larger, graded associations with HIVRB: moderate (WAOR=1.56; 95%CI: 1.49–1.62) and severe health issues (WAOR=2.15; 95%CI: 2.06–2.25) versus excellent health. Associations were stronger among females, particularly for severe HRQOL impairment (WAOR=2.48; 95%CI: 2.30–2.67), than males (WAOR=1.96; 95%CI: 1.86–2.08), with similar patterns across heavy drinking strata.

Stronger effect sizes for HRQOL suggest cumulative unhealthy days may better capture vulnerability to HIVRB than SRH. Integrating multidimensional health burden measures into HIV screening and prevention strategies may enhance risk identification.